Dr Graeme Hoddinott is a Senior Lecturer in Global Health at the University of Sydney. He is also an Extraordinary Associate Professor in paediatrics at Stellenbosch University. Much of his research experience is on tuberculosis, especially among children, adolescents, and their families. 

In this episode, we explore ground-breaking research on the preferences of children and adolescents in tuberculosis (TB) treatment and management, revealing surprising insights that could lead to better patient outcomes. We also discuss the hidden long-term effects of TB treatment in younger populations and highlight areas where further research is essential. 

Associate Professor Sarah Bernays, co-director of the Masters of Global Health program at the University of Sydney, leads a social science research program focused on community engagement in infectious disease prevention, treatment, and care. Her work emphasizes understanding how individuals, households, and communities respond to health adversity, risk, and vulnerability while fostering resilience and hope.

In this episode, we explored the perspectives of tuberculosis patients, the challenges they face in accessing and receiving clinical care, and methods to identify what truly matters to them. We also examined strategies for clinicians and researchers to enhance their approaches to interventions. Finally, we highlighted the importance of cultural contexts and the value of patient expertise in shaping effective care.

1. Person-centered and youth-oriented interventions to improve TB Care for adolescents and young adults: https://doi.org/10.1371/journal.pgph.0003659

Professor Guy Marks AO FAHMS is a distinguished respiratory and public health physician and environmental epidemiologist. Currently serving as the President and interim Executive Director of the International Union Against Tuberculosis and Lung Disease (The Union), he has led the Respiratory and Environmental Epidemiology group at the Woolcock Institute since 1997. His research primarily focuses on lung health, with particular emphasis on airway diseases, air pollution, and tuberculosis. Additionally, he is dedicated to capacity building in lung health research. 

In this episode, we delve into the essential factors for TB elimination, emphasizing the need for clinicians, researchers, and policymakers to focus on the infectious nature of TB. We explore the significance of large-scale active case finding, a strategy employed since the early 20th century, and discuss why targeted case-finding should be prioritized in middle- and low-burden countries where it proves most effective.

Summary (Unfortunately not included in the audio) 

Despite extensive eradication efforts comparable to malaria and HIV, TB remains a persistent public health issue. Guy indicated that current metrics suggest we are not on track to meet the 2030-2035 global TB eradication targets. 

Professor Marks highlights the primary factors required for TB elimination, with emphasis that as clinicians, researchers, and policymakers, we need to centre our approach to TB eradication on the basis infectious nature of TB. 

Since its use in the early 20th century in Western countries, large-scale active case finding remains a primary strategy in the management of TB. Guy indicates that targeted case-finding should be reserved for middle and low TB burden countries where it is more effective. 
 
Professor Mark's Vietnam-Based Research on TB Transmission shows that in high-burden TB countries: 

1. Most TB cases result from recent transmission, and are the largely responsible for driving the epidemic in these settings. 
2. Identifying and treating these recently diagnosed cases leads to a rapid reduction in TB incidence across the population. 

 Feasibility and cost remain as the prohibitive challenges for implementing molecular techniques widely in TB case identification. However, advances in radiographic technology are helping to bridge this gap, especially in high TB settings. 

 Professor Mark's suggests that the essential approach to achieving TB eradication will revolve around finding patients with TB and delivering efficient and effective healthcare.

The Union World Conference on Lung Health 2024 is just a few days away starting on 12 November 2024 in Bali, Indonesia, but it is still not too late to register. Be sure to explore the comprehensive Programme, full of the latest scientific breakthroughs in tuberculosis and lung disease.

 If you cannot make it to Bali, registered delegates have online access to most sessions as they happen or can watch at leisure.

Amanda Christensen joins us in this month's edition to discuss the critical impact of nurses in the fight against tuberculosis. Amanda is the Executive Director at the Australian Respiratory Council and is deeply experienced in the field of tuberculosis care.

We explored the ideal attributes of TB nurses, offering perspectives on tuberculosis both within Australia and across the Pacific. We discussed the importance of patient advocacy, examined the structure and management of TB programs within the Australian healthcare system, and highlighted the critical role TB nurses play in clinical and research settings. We also delved into the opportunities available for nurses to enter this impactful field.

Interviewer: Professor Greg Fox, ACTnet SC

Today we had the pleasure of being joined by Associate Professor Patrick Phillips from the University of California, who is the Co-Director of the UC Tuberculosis Research Advancement Center, Clinical & Population Health Science Core. Patrick has a wealth of statistical experience and specialises in the design, implementation, and optimisation of clinical trials for new treatments for drug-sensitive and drug-resistant tuberculosis.

Join us as we explore the rapidly evolving field of TB clinical trials and drug development. Discover the latest advancements in surrogate selection, novel Bayesian phase II designs, and the future of adaptive trial designs. We also delve into the critical clinician-statistician interface, highlighting the exciting opportunities for TB clinicians today.

• 10.1186/s12879-022-07846-w

Handaa Enkh Amgalan is an author, TB advocate and director of QA at the International Rescue Committee in Germany who has not only recently spoken at the UN TB High Level Meeting but also written an incredible memoir of her experience being diagnosed with severe pulmonary tuberculosis as a teenager growing up in Mongolia. Handaa gives an incredible insight into what it means to be diagnosed with such a stigmatising disease as a young woman; how it affect her, her family, and her dreams. This amazing story provides us insights into the devastating effects of stigma and sheds light on what we can do as health care workers to better support our patients.

Find Handaa's book at:
- https://www.amazon.co.uk/STIGMATIZED-Mongolian-Journey-Illness-Empowerment-ebook/dp/B0992QBHR2
- https://www.goodreads.com/book/show/58534082-stigmatized

Professor Adrian Martineau from the Queen Mary University London talks to us about the limitations of current latent TB infection diagnosis and how we can do better.  his research into whether we can use fragments of TB DNA found in bone marrow cells to better predict who should be treated with Tuberculosis Preventative Treatment.

REFERENCES
Martineau, Adrian R., et al. "Towards a molecular microbial blood test for tuberculosis infection." International Journal of Infectious Diseases (2024): 106988.

Belay, Mulugeta, et al. "Detection of Mycobacterium tuberculosis complex DNA in CD34-positive peripheral blood mononuclear cells of asymptomatic tuberculosis contacts: an observational study." The Lancet Microbe 2.6 (2021): e267-e275.

Repele, Federica, et al. "Detection of Mycobacterium tuberculosis DNA in CD34+ peripheral blood mononuclear cells of adults with tuberculosis infection and disease." International Journal of Infectious Diseases 141 (2024): 106999.

Today we discuss the MTBVAC with Dr Montañés. MTBVAC is an attenuated vaccine from a human mycobacterial isolate which has just progressed to a phase 3 trial and shown very promising results in the phase 2 study. Dr Montañés has been involved in this project for over a decade and has an incredible insight into the development and promise of this vaccine for global TB epidemiology.

References
Martín, Carlos, et al. "MTBVAC, a live TB vaccine poised to initiate efficacy trials 100 years after BCG." Vaccine 39.50 (2021): 7277-7285.

Achkar, Jacqueline M. "Prospects and challenges of a new live tuberculosis vaccine." The Lancet Respiratory Medicine 7.9 (2019): 723-725.

Arbues, Ainhoa, et al. "Construction, characterization and preclinical evaluation of MTBVAC, the first live-attenuated M. tuberculosis-based vaccine to enter clinical trials." Vaccine 31.42 (2013): 4867-4873.

Tameris, Michele, et al. "Live-attenuated Mycobacterium tuberculosis vaccine MTBVAC versus BCG in adults and neonates: a randomised controlled, double-blind dose-escalation trial." The lancet Respiratory medicine 7.9 (2019): 757-770.

Spertini, François, et al. "Safety of human immunisation with a live-attenuated Mycobacterium tuberculosis vaccine: a randomised, double-blind, controlled phase I trial." The lancet Respiratory medicine 3.12 (2015): 953-962.

Gonzalo-Asensio, Jesus, et al. "MTBVAC: attenuating the human pathogen of tuberculosis (TB) toward a promising vaccine against the TB epidemic." Frontiers in immunology 8 (2017): 296893.

Prof Greg Fox speaks with Prof Philip Hill about TB household contact tracing and building research capacity in TB.

Prof Hill is an ID specialist and public health physician who did his PhD in TB Epidemiology. He is the current McAuley Chair in International Health as well as being Founding Direction & Co-Director of the Centre for International Health at the University of Otago.

References
1) Martinez, Leonardo, et al. "The risk of tuberculosis in children after close exposure: a systematic review and individual-participant meta-analysis." The Lancet 395.10228 (2020): 973-984.
2) Hill, Philip C., et al. "Incidence of tuberculosis and the predictive value of ELISPOT and Mantoux tests in Gambian case contacts." PLoS One 3.1 (2008): e1379.
3) Martinez, Leonardo, et al. "Transmission of Mycobacterium tuberculosis in households and the community: a systematic review and meta-analysis." American journal of epidemiology 185.12 (2017): 1327-1339.
4) Martinez, Leonardo, et al. "Paediatric tuberculosis transmission outside the household: challenging historical paradigms to inform future public health strategies." The Lancet Respiratory Medicine 7.6 (2019): 544-552.
5) Hill, Philip C., and Martin OC Ota. "Tuberculosis case-contact research in endemic tropical settings: design, conduct, and relevance to other infectious diseases." The Lancet infectious diseases 10.10 (2010): 723-732.
6) Alisjahbana, Bachti, et al. "Are neighbourhoods of tuberculosis cases a high-risk population for active intervention? A protocol for tuberculosis active case finding." Plos one 16.8 (2021): e0256043.

Today we speak with Dr Guglielmetti about the END-TB trial which looks at new all oral regimens for MDR-TB.

REFERENCES
1) https://endtb.org/
2) Nyang’wa, Bern-Thomas, et al. "A 24-week, all-oral regimen for rifampin-resistant tuberculosis." New England Journal of Medicine 387.25 (2022): 2331-2343.
3) Conradie, Francesca, et al. "Treatment of highly drug-resistant pulmonary tuberculosis." New England Journal of Medicine 382.10 (2020): 893-902.
4) Diacon, Andreas H., et al. "Multidrug-resistant tuberculosis and culture conversion with bedaquiline." New England Journal of Medicine 371.8 (2014): 723-732.
5) Gler, Maria Tarcela, et al. "Delamanid for multidrug-resistant pulmonary tuberculosis." New England Journal of Medicine 366.23 (2012): 2151-2160.
6) Ahmad, Nafees, et al. "Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis." The Lancet 392.10150 (2018): 821-834.
7) Lan, Zhiyi, et al. "Drug-associated adverse events in the treatment of multidrug-resistant tuberculosis: an individual patient data meta-analysis." The Lancet Respiratory Medicine 8.4 (2020): 383-394.
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